In this proposal, we hope to characterize and study the mechanism of gonadal dysfunction in men and women with chronic renal failure. Special emphasis will be placed on uncovering adnormalities of the hypothalamo-pituitary control axis. Circulating levels of gonadal steroids and gonadotropins will be measured and seminal fluid analyses will be done during the steady state of renal failure, after pharmacologic maneuvers, and post-renal transplantation. Serum prolactin levels will be measured in the basal state and after administration of TRH and L-DOPA. Attempts will be made to correct the hormonal deficiency or imbalance with physiologic and pharmacologic agents including estrogen, testosterone, clomiphene citrate, bromo-ergocryptine, and cyproheptidine. The sexual maturation of children with renal failure will be evaluated by detailed physical examination as well as by measurements of circulating levels of gonadal and adrenal steroids. Basal gonadotropins and gonadotropic response to clomiphene citrate will also be determined in an attempted to assess the integrity of the hypothalamus. A uremic model in rats will be used for the study of testosterone production and macromolecular synthesis in the testicular tissue. Such a study will be carried out both in vivo and in vitro, using the appropriate labeled precursors.